A dynamic relationship is hypothesized between the auditory periphery and the regulation of synaptic biochemistry in pathways of the central auditory nervous system. This predicts that changes in the acoustic efficacy of the ear, for example, after the cochlear trauma or long exposure to abnormally low or high levels of sound, should adjust the synaptic biochemistry of auditory pathways. Persistent changes of synaptic structure in the medial nucleus of the trapezoid body and of neuronal discharge in the inferior colliculus, medial geniculate nucleus, and auditory cortex were reported after procedures that decrease the acoustic efficacy of one ear. These changes may reflect a regulatory process that begins in the ascending brain stem auditory pathways. Knowledge of these phenomena will be valuable in understanding the synaptic basis of auditory functions, controlling pathology, and rehabilitating the central auditory system after insult. We propose to elucidate the hypothesized regulatory relationship. FIRST, we will identify the ascending auditory brain stem projections that use transmitters such as glutamate, aspartate, homocysteic acid, cysteine sulfanilic acid, GABA, glycine, and acetylcholine. Transmitters have been suggested for only one or two of the ascending auditory pathways. To determine the transmitters used by the others, ascending tracts will be lesioned to destroy their synaptic endings. At each projection site, we will measure changes in the evoked release and the high affinity uptake of the putative transmitters and quantify the binding activity of synaptic receptors. SECOND, we will determine the effect of cochlear lesions on the synaptic transmitter biochemistry in the brain stem auditory nuclei. High frequency hearing loss will be produced by acoustic trauma and surgical lesions of the cochlea. Then, synaptic biochemical activities, such as transmitter release, high-affinity uptake, and receptor binding, will be compared in the projection sites of the ascending auditory pathways of hearing-impaired and unlesioned cases. THIRD, we will determine the effect of exposure to different levels of sound on the synaptic transmitter biochemistry in the brain stem auditory nuclei. Three levels of environmental noise will provide different levels of cochlear activity without cochlear damage. We will compare synaptic biochemical activities in animals with bilateral ossiculectomies, intact animals kept in a 'normal' environment, and intact animals kept in a 'noisy' environment.